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Leonid Livshitz

Publications and source records attributed to Leonid Livshitz.

5 recordsLinked to original sources
PubMed2006

Kinetic properties of the cardiac L-type Ca2+ channel and its role in myocyte electrophysiology: a theoretical investigation.

The L-type Ca(2+) channel (Ca(V)1.2) plays an important role in action potential (AP) generation, morphology, and duration (APD) and is the primary source of triggering Ca(2+) for the initiation of Ca(2+)-induced Ca(2+)-release in cardiac myocytes. In this article we present: 1), a detailed kinetic model of Ca(V)1.2, which is incorporated into a model of the ventricular mycoyte where it interacts with a kinetic model of the ryanodine receptor in a restricted subcellular space; 2), evaluation of the contribution of voltage-dependent inactivation (VDI) and Ca(2+)-dependent inactivation (CDI) to total inactivation of Ca(V)1.2; and 3), description of dynamic Ca(V)1.2 and ryanodine receptor channel-state occupancy during the AP. Results are: 1), the Ca(V)1.2 model reproduces experimental single-channel and macroscopic-current data; 2), the model reproduces rate dependence of APD, [Na(+)](i), and the Ca(2+)-transient (CaT), and restitution of APD and CaT during premature stimuli; 3), CDI of Ca(V)1.2 is sensitive to Ca(2+) that enters the subspace through the channel and from SR release. The relative contributions of these Ca(2+) sources to total CDI during the AP vary with time after depolarization, switching from early SR dominance to late Ca(V)1.2 dominance. 4), The relative contribution of CDI to total inactivation of Ca(V)1.2 is greater at negative potentials, when VDI is weak; and 5), loss of VDI due to the Ca(V)1.2 mutation G406R (linked to the Timothy syndrome) results in APD prolongation and increased CaT.

Action Potentials↗
PubMed2004

Augmentation of dilated failing left ventricular stroke work by a physiological cardiac assist device.

A novel physiological cardiac assist device (PCAD), otherwise known as the LEVRAM assist device, which is synchronized with the heartbeat, was developed to assist the left ventricle (LV) in chronic heart failure (CHF). The PCAD utilizes a single cannula, which is inserted in less than 15 s through the apex of the beating LV by means of a specially designed device. Blood is withdrawn from the LV into the PCAD in diastole and is injected back to the LV, through the same cannula, during the systolic ejection phase, thereby augmenting stroke volume (SV) and stroke work (SW). CHF with dilated LV was induced in sheep by successive intracoronary injections of 100-microm beads. The sheep (92.2 +/- 25.9 kg, n = 5) developed stable CHF with increased LV end-diastolic diameter (69.4 +/- 3.3 mm) and end-diastolic volume (LVEDV = 239 +/- 32 mL), with severely reduced ejection fraction (23.8 +/- 7.6%), as well as mild-to-moderate mitral regurgitation. The sheep were anesthetized, and the heart was exposed by left thoracotomy. Pressure was measured in the LV and aorta (Millar). The SV was measured by flow meters and the LV volume by sonocrystals. Assist was provided every 10 regular beats, and the assisted beats were compared with the preceding unassisted beats, at the same LVEDV. The PCAD displaced 13.6 +/- 3.4 mL, less than 8% of LVEDV. Added SW was calculated from the assisted and control pressure-volume loops. The efficiency, defined as an increase in SW divided by the mechanical work of the PCAD, was 85.4 +/- 16.9%. We conclude that the PCAD, working with a small displaced blood volume in synchrony with the heartbeat, efficiently augments the SW of the dilated failing LV. The PCAD is suggested for use as a permanent implantable device in CHF.

Animals↗
PubMed2003

Force, sarcomere shortening velocity and ATPase activity.

UNLABELLED: We have tested the hypothesis that the transition rate (G) of the cardiac XB from the strong force generating state to the weak state is a linear function V of the sarcomere (VSL); furthermore, we tested whether the ATPase rate of the two isoforms of myosin can be held responsible for the difference between V0 of rat cardiac trabeculae containing V1 isomyosin versus those containing V3 isomyosin. METHODS: V1 isomyosin was induced by thyroid hormone treatment of the rats for 2 weeks, V3 isomyosin by PTU treatment for 1 month. Force was measured with a strain gauge in trabeculae from the rat right ventricle in K-H solution ([Ca]o=1.5 mM, 25 degrees C). Sarcomere length (SL) was measured with laser diffraction techniques. Twitch force at constant SL, and the force response to shortening at constant VSL (0-8 microm/s; deltaSL 50-100 nm) were measured at varied time during the twitch. RESULTS: The force response to shortening consisted of a fast initial exponential decline (tau = 2 ms) followed by a slow decrease of F. The instantaneous difference (deltaF) between isometric force (FM) and the declining force depended on shortening duration (deltat), VSL and instantaneous FM: deltaF = G1 x FM x deltat x VSL x (1-VSL/VMAX), where VMAX is the unloaded VSL and G1 was 6.15 +/- 2.12 microm(-1) (mean +/- s.d.; n=6). deltaF/FM was independent of the time onset of shortening. G1 of V1 and V3 trabeculae did not differ. V0 of V1 and V3 trabeculae differed 2-2.5 fold, as did both the ATPase rate and the velocity of actin sliding in a motility assay of the myosin purified from V1 or V3 hearts. The temperature dependence of the ATPase rate (Q10: 4.03 and 4.33, respectively; n.s.) was similar to that of V0 that has previously been reported for predominantly V1 trabeculae. Cross-linking of actin to myosin with the short chain cross linker EDC increased the ATPase rate of the two isomyosins (200-fold and 600-fold respectively) to exactly the same final level and reduced their Q10 by 50%. CONCLUSION: The linear interrelation between deltaF and VSL is consistent with feedback, whereby XB kinetics depends on VSL. This feedback provides an integrated description of cardiac muscle mechanics and energetics. The results, also, suggests that it is unlikely that the hydrolytic domain of the cross bridge determines V0 and warrant ongoing experiments to investigate the role of the actin binding domain of the XB in cardiac sarcomere kinetics. In order to further investigate the role of the actin binding domain, we have expressed chimeric cardiac myosin, co-assembled with MLC, by mutual substitution of actin binding loop on alpha MHC and beta MHC.

Actins↗